WASHINGTON -- The FDA has approved a once-monthly injectable depot formulation of buprenorphine (Sublocade) for moderate-to-severe opioid use disorder patients who've been on the sublingual formulation for at least a week, .
The product can only be dispensed by healthcare professionals under a risk evaluation and mitigation strategy (REMS), and it comes with a boxed warning on the risks of intravenous administration -- including occlusion, tissue damage, or embolus. It is only intended to be injected subcutaneously for depot formation.
Manufactured by Indivior -- a spinoff from Reckitt Benckiser -- the drug's safety and efficacy were established in one randomized controlled trial and one open-label trial, totaling 848 adults with opioid use disorder.
Those who got the drug had more weeks without positive urine screens or self-reported opioid use, and a higher proportion had no evidence of illicit opioid use through the treatment period, FDA said.
The most common side effects included constipation, nausea, vomiting, headache, drowsiness, injection site pain, pruritus at the injection site, and abnormal liver function tests.
During an FDA advisory committee hearing last month, panelists backed the product's approval, but some raised concern about a lack of evidence for benefit with a high-dose regimen (300 mg for the initial dose and 300 mg for maintenance).
Indivior said a lower 100-mg dose for maintenance treatment, also tested in the trials, will be available. The recommended dose will be two initial monthly doses of 300 mg followed by maintenance treatment with 100 mg per month, the company said.
The wholesale acquisition cost will be $1,580 per injection, irrespective of dosage, .
The agency is requiring postmarketing studies to assess several questions: which patients would benefit from a higher dosing regimen; whether Sublocade can be safely initiated without a dose stabilization period of sublingual buprenorphine; whether it's feasible to administer Sublocade at a longer inter-dose interval than monthly; and how a process for transitioning patients with long-term stability on a transmucosal buprenorphine dose to a monthly dose of Sublocade without the use of a higher dose for the first two months of treatment can be established.
In a , FDA Commissioner Scott Gottlieb, MD, said the agency plans to issue a guidance document on approving depot formulations for buprenorphine for opioid dependence. A second guidance will focus on describing how to establish additional endpoints that may help facilitate development of better treatments, he said.
Gottlieb promoted other FDA opioid initiatives in his statement, including a greater push to make medication-assisted treatment (MAT) more accessible. That involves devising a way to create a labeling claim to make MAT available at the point of care, when a patient presents with overdose, which could lead to a reduction in death over a population: "Such an effort would be a first for the FDA," he said.
Gottlieb added that FDA recently revised the labels of buprenorphine products to state that evidence shows people may need treatment for long periods and may even need a lifetime of treatment. FDA is currently evaluating this type of labeling for naltrexone and methadone as well, he said.